Treatment planning facilitates clinical decision making for hyperthermia treatments.

Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated.Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments.HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available.Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.

Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich's "magic (nano)bullet" for cancer theranostics?

Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future.

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

An audit of postoperative radiotherapy after non-curative resection for cancer of the oesophagus.

AIMS: The role of postoperative radiotherapy (PORT) after non-curative resections for cancer oesophagus is not well defined. A policy of offering PORT after non-curative resections for cancer oesophagus has been followed at our institution, and we report an audit of our experience. MATERIAL AND METHODS: Between March 1990 and September 2002, 139 patients underwent resections for cancer oesophagus. Of these, 86 patients received PORT to a dose of 45-50.4 Gy/25-28 fractions. Eleven of these patients also received concurrent and adjuvant 5-fluorouracil (5-FU). Disease-free survival and overall survival were computed from the day of surgery using the Kaplan-Meier method. RESULTS: Seventy-six per cent (65/86) of patients had squamous cell carcinoma and 69% (59/86) of patients had tumours in the lower-third of the oesophagus. The median interval between surgery and PORT was 41 days, and 93% of patients received doses as planned. Strictures at the anastomotic site and ulcerations in the stomach mucosa were seen in 17% and 5% of patients, respectively. The median and 5-year disease-free survival was 12 months (95% CI 9.9-14.1) and 14%; whereas the median and 5-year overall survival was 17 months (95% CI 12.4-21.6) and 17%, respectively. Local and distant failures were seen in 29% and 45% of patients, respectively. CONCLUSIONS: PORT, after a non-curative resection of cancer oesophagus, is well tolerated with acceptable morbidity and survival.

Summated chemotherapy dose-intensity versus loco-regional response in locally advanced breast cancer: its possible implications.

BACKGROUND: Summated dose-intensity (SDI) of chemotherapy regimen could influence the outcome in malignancies. AIMS: To evaluate the implication of SDI and identify key drugs for loco-regional response in locally advanced breast cancer (LABC). SETTINGS AND DESIGN: This retrospective study was based on audit of records of LABC patients who had received neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: Actual unit dose-intensity (UDI) of each drug and corresponding SDI of every doxorubicin (n=116 cycles) or non-doxorubicin (n=110 cycles) based NACT received by 42 patients of LABC were summated. Cumulative dose-intensity (CDI) for individual drugs and cumulative SDI (CSDI) for the entire course of NACT were estimated and correlated with quantum of primary tumor, axillary and supraclavicular nodal responses. STATISTICAL ANALYSIS USED: Two-sided chi-square, t-test, step-wise regression was used. RESULTS: Dose-response curve between CSDI and corresponding responses for both primary and lymph nodes were sigmoid in shape for both doxorubicin or non-doxorubicin based NACT. Curves were best fitted using a cubic fit for all patients (r2 = 0.82, 0.84 and 0.93 for primary tumor, axillary and supraclavicular lymph nodes respectively). CSDI emerged as an important prognosticators for both primary (P<0.001) and nodal (P<0.001) responses. Individually, CDI of 5-fluorouracil for primary (P<0.001), CDIs of doxorubicin (P<0.001) and methotrexate (P=0.006) for axillary nodes and CDI of cyclophosphamide (P=0.001) for supraclavicular nodes were significant. CONCLUSIONS: Loco-regional responses in LABC are dependent on CSDI of NACT regimen. Drugs for high-dose intensification protocols could be identified and chosen based on the impact of CDI of individual drugs in NACT.

Feasibility of non-cisplatin-based induction chemotherapy and concurrent chemoradiotherapy in advanced head and neck cancer.

The purpose of the present study was to determine the safety and efficacy of induction chemotherapy followed by concomitant chemoradiotherapy. Thirty-eight patients were randomised to receive induction chemotherapy, consisting of cyclophosphamide and methotrexate followed by concomitant 5-fluorouracil and irradiation (study group) or irradiation alone (control group). There were non-significant differences in the initial tumor clearance rates in the two groups. Median disease-free survival (in complete responders) was 17 months (6-60+) vs 11 months (5-60+) (p = 0.407) and overall survival 11 months (1-60+) vs 14 months (2-60+) (p = 0.428) in the study and control groups respectively. Acute morbidity and deaths during intervention were higher in the study group (p = 0.007). This study suggests that induction along with concomitant chemoradiotherapy is too toxic for routine use and also fails to provide a survival benefit.